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Trial record 9 of 167 for:    gastroenterology | Recruiting | United States

Genotype-supported Versus Conventional Proton Pump Inhibitor Dosing

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2016 by University of Florida
Sponsor:
Collaborators:
Nemours Children's Hospital
National Human Genome Research Institute (NHGRI)
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT02930824
First received: October 10, 2016
Last updated: December 16, 2016
Last verified: December 2016
  Purpose
Investigators will conduct a comparative effectiveness study of genotype-supported vs. conventional PPI dosing. Patients presenting with Gastroesophageal Reflux Disease (GERD) or dyspepsia symptoms and either 1) being initiated on proton pump inhibitor (PPI) therapy or 2) with continued symptoms on current PPI therapy will be recruited from gastroenterology clinics and randomized to a genotype-supported versus conventional PPI therapy management strategy.

Condition Intervention Phase
Gastroesophageal Reflux Disease
Genetic: CYP2C19 genotyping
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Screening
Official Title: Implementing Genomics in Practice (IGNITE) Proof of Concept Study: CYP2C19 Genotype-supported Versus Conventional Proton Pump Inhibitor Dosing

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • Reflux Disease Questionnaire (RDQ) [ Time Frame: Change from baseline and 12 weeks ]
    The RDQ was developed to monitor treatment response over time and evaluates 6 symptoms (12 items) covering 3 domains: heartburn, regurgitation, and upper abdominal pain. Each symptom is evaluated using a 6-point Likert scale to assess frequency and severity over the previous week. Each symptom is rated from 1 (did not have) to 6 (severe), and the RDQ mean score is calculated as the mean response to the 12 items. The RDQ mean score thus ranges from 1 to 6 and has been psycho-metrically validated.

  • Global Overall Symptom scale (GOS) [ Time Frame: Change from baseline and 12 weeks ]
    The GOS scale evaluates 18 symptoms, with each rated from 1 (no problem) to 7 (very severe). The mean score is calculated as the mean response to the 18 items, with mean scores ranging from 1 to 7.


Estimated Enrollment: 180
Study Start Date: December 2016
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Genotype guided treatment
For patients randomized to the genotype-supported arm a CYP2C19 genotype will be provided to physicians to assist in dosing.
Genetic: CYP2C19 genotyping
All proton pump inhibitors are metabolized in part by the CYP2C19 enzyme, which is encoded by the highly polymorphic CYP2C19 gene. Based on variations within this gene the effectiveness of the drug may be reduced.
No Intervention: Conventional treatment
For patients randomized to the genotype-supported arm a no genotype will be provided to physicians to assist in dosing.

Detailed Description:
The efficacy of proton pump inhibitors (PPIs) is highly dependent on plasma concentrations achieved following drug administration. All PPIs are metabolized in part by the CYP2C19 enzyme, which is encoded by the highly polymorphic CYP2C19 gene. Depending on the CYP2C19 genotype, individuals are classified into different metabolizer phenotypes: poor metabolizers (PM, 2 loss-of-function CYP2C19 alleles); intermediate metabolizers (IM, one loss-of-function allele); normal metabolizers (NM, no loss or gain-of-function alleles); rapid metabolizer (RM; one gain-of-function allele) and ultra-rapid metabolizers (UM, two gain-of function-alleles). Genetic variants in CYP2C19 are known to profoundly influence PPI plasma concentrations and consequently, response to PPI therapy. For example, individuals classified as either RM or UM have lower PPI concentrations compared to NM or loss-of-function (LOF) allele carriers, respond poorly to PPI therapy, and some fail to respond even when the PPI dose is increased. The investigators hypothesize that genotype-supported PPI dosing will lead to better GERD control and improvement in severity of dyspepsia symptoms compared to conventional dosing. The investigators will conduct a comparative effectiveness study of genotype-supported vs. conventional PPI dosing. Patients presenting with GERD or dyspepsia symptoms and either 1) being initiated on PPI therapy or 2) with continued symptoms on current PPI therapy will be recruited from gastroenterology clinics and randomized to a genotype-supported versus conventional PPI therapy management strategy. The investigators will integrate individual CYP2C19 genotype information into dosing decisions for the genotype-supported arm and compare change in symptom control from baseline to the end of the study between study arms. Given that PPI efficacy is related to PPI exposure and to metabolizer phenotype, individualizing treatment using CYP2C19 genotype-supported dosing is expected to improve symptom management. The investigators will also evaluate patient and clinician knowledge and attitudes about pharmacogenetics testing and physician acceptance of genetic information into clinical practice. Finally, the investigators will collect preliminary data on the potential impact of CYP2C19-supported PPI dosing on adverse event rates.
  Eligibility

Ages Eligible for Study:   18 Years to 100 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18 years of age or older
  • Gastroesophageal Reflux Disease symptoms
  • Being initiated on PPI therapy OR continues to have symptoms despite PPI therapy

Exclusion Criteria:

  • Extensive esophageal or gastric surgery
  • Any chronic illness that would interfere with the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02930824

Contacts
Contact: Larisa Cavallari, PharmD (352) 273-8245 lcavallari@cop.ufl.edu

Locations
United States, Florida
University of Florida Recruiting
Gainesville, Florida, United States, 32610
Contact: Larisa Cavallari, PharmD    352-273-8245    lcavallari@cop.ufl.edu   
Nemours Children's Hospital Recruiting
Orlando, Florida, United States, 32827
Contact: James P Franciosi, MD    407-567-3832    jpfranciosi@yahoo.com   
Sponsors and Collaborators
University of Florida
Nemours Children's Hospital
National Human Genome Research Institute (NHGRI)
Investigators
Principal Investigator: Larisa Cavallari, PharmD University of Florida
Principal Investigator: James P Franciosi, MD Nemours Children's Hospital
  More Information

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT02930824     History of Changes
Other Study ID Numbers: IRB201601774
U01HG007269 ( US NIH Grant/Contract Award Number )
Study First Received: October 10, 2016
Last Updated: December 16, 2016
Individual Participant Data  
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Gastroesophageal Reflux
Esophageal Motility Disorders
Deglutition Disorders
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 25, 2017